Cognitive profile of subcortical ischaemic vascular disease.

OBJECTIVES: Subcortical ischaemic vascular disease (SIVD) is a subtype of vascular cognitive impairment characterised by extensive white matter lesions and multiple lacunar infarcts. Radiologically defined diagnostic criteria for SIVD have been introduced, but only a few studies have presented empirical data on its clinical and cognitive features. The aim of this study is to describe in detail the neuropsychological characteristics of patients with SIVD from a large well defined stroke cohort. METHODS: A sample of 323 consecutive patients with ischaemic stroke, aged 55-85 years, was investigated using neuropsychological examination and magnetic resonance imaging (MRI). Patients fulfilling the MRI criteria of SIVD (n = 85) were compared to the other stroke patients (n = 238) and to normal control subjects (n = 38). RESULTS: Cognitive performance of the SIVD group was inferior to that of the normal control group throughout all domains. As compared to the other stroke patients, the SIVD group performed significantly worse in tests measuring executive functions and delayed memory recall. Adjusting for depression had no effect on these results. Instead, after controlling for medial temporal lobe atrophy, the differences disappeared for delayed memory but remained significant for executive functions. CONCLUSION: Executive deficits are the most prominent cognitive characteristic associated with SIVD. Patients with SIVD also exhibit subtle deficits in delayed memory, which is explained in part by medial temporal lobe atrophy. Cognitive and mood changes seem to be parallel but independent processes related to SIVD. The results support the concept of SIVD as a separate clinical entity.

White matter hyperintensities as a predictor of neuropsychological deficits post-stroke.

OBJECTIVES: Cerebral white matter hyperintensities (WMHs) on magnetic resonance imaging (MRI) are a recognised risk factor for post-stroke dementia. Their specific relations to cognitive impairment are still not well known. The purpose of this study was to explore how the severity and location of WMHs predict neuropsychological test performance in the context of other brain lesions in elderly stroke patients. METHODS: In the Helsinki Stroke Aging Memory Study, 323 patients, aged from 55 to 85 years, completed a detailed neuropsychological test battery and MRI 3 months after an ischaemic stroke. The demographic and MRI predictors of cognition were studied with sequential linear regression analyses. RESULTS: After age, education and total infarct volume were controlled for, the overall degree of WMHs predicted poor performance in tests of mental speed, executive functions, memory, and visuospatial functions, but not in those of short term memory storage or verbal conceptualisation. However, the contribution of separate white matter regions was relatively low. Only the lesions along the bodies of lateral ventricles were independently associated with speed and executive measures. Additionally, general cortical atrophy clearly predicted a wide range of cognitive deficits while infarct volume had less relevance. Further analyses revealed that executive functions act as a strong mediator between the relationship of WMHs to memory and visuospatial functions. CONCLUSIONS: The degree of WMHs is independently related to post-stroke cognitive decline. The most affected cognitive domains seem to be executive functions and speed of mental processing, which may lead to secondary deficits of memory and visuospatial functions.

Medial temporal lobe atrophy and memory deficits in elderly stroke patients.

Medial temporal lobe atrophy (MTA) and its role in memory deficits have been studied extensively in patients with various dementias and non-degenerative neurologic diseases. In stroke patients MTA is a significant risk factor for dementia. However, its role in memory decline in non-demented stroke patients is not yet known. Our aim was to evaluate the relationship between MTA and cognitive functions in a large cohort of elderly patients, who underwent a comprehensive neuropsychologic examination and magnetic resonance imaging 3 months after an ischemic stroke. The study sample (n = 260) was divided into three groups according to the severity of MTA. After adjusting for age, volume of infarcts and cortical atrophy, we found that patients with moderate to severe MTA performed significantly worse in tests of learning, story recall, visual reproduction, block design and mental speed. In contrast, the groups did not differ in tests of digit span, flexibility, verbal fluency and conceptualization. Our conclusion is that in aged stroke patients, MTA is associated with poor performance in specific cognitive domains. The most vulnerable domains are memory and visuospatial functions, whereas verbal and executive functions seem to be unrelated to MTA.

MRI correlates of executive dysfunction in patients with ischaemic stroke.

Executive dysfunction (ED) may lead to problem behaviour and impaired activities of daily living in many neuropsychiatric disorders, but the neuroanatomical correlates of ED are still not well known. Different aspects of executive functions were studied by widely used neuropsychological tests in 214 elderly patients 3 months after ischaemic stroke, and a sum score of eight different measures was counted in each patient. The number and site of brain infarcts as well as severity and location of white matter lesions (WMLs) and brain atrophy on magnetic resonance imaging were recorded and compared between patients with and without ED. ED was present in 73 (34.1%) of the 214 patients. The mean frequency of brain infarcts in the brain and in the left hemisphere was higher in the patients with ED. Lesions affecting the frontal-subcortical circuits (e.g. pallidum, corona radiata or centrum semiovale) were more frequent in patients with ED than in those without. Also, patients with pontine brain infarcts frequently had ED, but this may have been due to more extensive ischaemic changes in these patients in general. Mean number of brain infarcts affecting the pons and posterior centrum semiovale on the left side, moderate to severe medial temporal atrophy, the Fazekas white matter score, the Mini-Mental State Examination score and low education were independent correlates of ED. Brain infarcts and WML affecting the frontal-subcortical circuits or the pons may increase risk for ED in stroke patients.

Post-stroke depression, executive dysfunction and functional outcome.

The early diagnosis of vascular cognitive impairment has been challenged and executive control function has been suggested to be a rational basis for the diagnosis of vascular dementia. We sought to examine the correlates of executive dysfunction in a well-defined stroke cohort. A group of 256 patients from a consecutive cohort of 486 patients with ischaemic stroke, aged 55-85 years, was subjected to a comprehensive neuropsychological examination 3-4 months after ischaemic stroke and 188 of them in addition to detailed psychiatric examination. Basic and complex activities of daily living (ADLs) (bADLs and cADLs) post-stroke were assessed. The DSM-III-R criteria were used for the diagnosis of the depressive disorders. Altogether 40.6% (n=104) of the patients had executive dysfunction. The patients with executive dysfunction were older, had lower level of education, were more often dependent, did worse in bADLs and cADLs, had more often DSM-III dementia, had worse cognition as measured by Mini Mental State Examination (MMSE) and were more depressed as measured by the BECK depression scale, but not with the more detailed psychiatric evaluation. They had more often stroke in the anterior circulation and less often in the posterior circulation. The independent correlates of executive dysfunction were cADLs (OR 1.1, 95% CI 1.03-1.16), each point of worsening in cognition by MMSE (OR 1.7, 95% CI 1.42-1.97) and stroke in the posterior circulation area (OR 0.4, 95% CI 0.18-0.84). Clinically significant executive dysfunction is frequent after ischaemic stroke and is closely connected with cADLs and to overall cognitive status but could be distinguished from depression by detailed neuropsychological examination. Executive measures may detect patients at risk of dementia and disability post-stroke.

Evaluation of various methods of assessing symptoms of cognitive impairment and dementia.

BACKGROUND AND PURPOSE: The effect of different diagnostic criteria for detecting dementia in both epidemiological and stroke cohort studies has been shown, but comparison between different assessment methods has only seldom been done. We compared both assessment methods and diagnostic criteria for dementia in a large well-defined stroke cohort. SUBJECT AND METHODS: A group of 227 of 486 patients aged 55 to 85 years who 3 months after ischemic stroke completed a comprehensive neuropsychological test battery, structured clinical mental status examination of defined cognitive domains with expanded Mini-Mental State Examination. The criteria for dementia were those of the Diagnostic and Statistical Manual of Mental Disorders (DSM-III, DSM-III-R) and the National Institute of Neurological Disorders and Stroke-Associated Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN). RESULTS: The main differences between clinical and neuropsychological examinations were seen in memory functions: clinically 24.7% and neuropsychologically 54.2% had impairment in short-term memory and 10.4% versus 5.3% in long-term memory. Accordingly, the prevalence of dementia varied greatly: It was clinically 14.1% by DSM-III, 9.7% by DSM-III-R and 8.4% by NINDS-AIREN criteria. The corresponding frequencies based on neuropsychological evaluation were 27.3%, 4.0% and 25.6%. Between these 3 diagnostic criteria the concordance varied in clinical testing between 59.4%-68.8% (kappa 0.72-0.79) and in neuropsychological testing between 14.5%-81.1% (kappa 0.20-0.86). The concordance between clinical and neuropsychological testing was 56.8% (kappa 0.42) by DSM-III, 31.6% (kappa 0.35) by DSM-III-R and 25.5% (kappa 0.24) by NINDS-AIREN. CONCLUSIONS: The frequency of poststroke dementia and cognitive decline varied sharply when different systems of diagnostic classification and methods were used. This may have serious influences on investigation and treatment of patients. We underline the importance of further debate and studies to refine the categories of cognitive impairment used in the setting of CVD.

Are negative mood states associated with cognitive function in newly diagnosed patients with epilepsy?

PURPOSE: The association of self-reported subclinical depressive symptoms and negative mood states with cognitive functioning was evaluated in 51 consecutive newly diagnosed adult persons with epilepsy. METHODS: Emotional state was assessed with Profile of Mood States (POMS) and Brief Depression Scale (BDS) and was correlated with a battery of neuropsychological tests. RESULTS: Patients with epilepsy reported more depressive symptoms in BDS than in controls. They also had more feeling of bewilderment and less vigor on POMS. Higher scores in BDS and in POMS inefficiency scale were associated with slower nondominant hand tapping, but emotional state did not correlate with cognitive measures within the epilepsy group. CONCLUSIONS: Self-reported symptoms of depression and negative mood states were not extensively or significantly associated with cognitive function, and they do not explain the cognitive impairments observed in cognition in newly diagnosed patients with epilepsy.

Memory and metamemory functioning among depressed patients.

Memory and metamemory functioning were studied among 30 adult patients suffering from major depression. The results indicate that, besides showing signs of cognitive slowing, the patients were especially vulnerable to visual memory impairment, whereas verbal, short-term memory, and recall by recognition were more often unaffected. The patients whose depression was characterized by physiological symptoms, such as loss of appetite and sleep disturbances, showed impairment in traditional short-term memory measures, whereas there was no firm connection between cognitive or behavioral depressive symptoms and memory functioning. The depressive patients' generalized view of their memory capability was strongly underestimated, whereas online metamemory accuracy by which one perceives and makes inferences about one's performance was adequate.

Executive functions and speed of mental processing in elderly patients with frontal or nonfrontal ischemic stroke.

Impairments in executive functions have been related to aging and frontal lobe lesions. Aging also causes slowing of mental processing. We examined whether ischemic stroke in the frontal brain area results in dysexecutive syndrome, or whether the frontal stroke causes increased slowing of mental processing. Neurological, radiological and neuropsychological examinations were carried out 3 months post-stroke on 250 ischemic stroke patients (55-85 years) and on 39 healthy control subjects. Of the patients, 62 had frontal and 188 had nonfrontal lesions. The neuropsychological examination comprised several cognitive domains, including tests considered to measure executive functions. The frontal group was slower than the nonfrontal group in tasks measuring speed of mental processing which were time-limited (Trail Making A, Stroop dots and fluency). They were also inferior in the Digit Span backwards task. There were no differences between the groups in other cognitive domains, nor in some tests which are considered to be measures of executive functions (e.g. WCST). Impairments in executive functions were evident in both the frontal and the nonfrontal groups compared with the controls, but no dysexecutive syndrome specifically related to frontal lesions was found. Frontal stroke related mainly to the slowing of mental processing.

Effects of alcohol, zolpidem, and some other sedatives and hypnotics on human performance and memory.

Zolpidem (Zol), an omega1-agonist, acts via GABA(A) receptors but may differ qualitatively from diazepam (Dz) and other benzodiazepines (BZDs). We conducted a placebo-controlled, randomized, double-blind, and crossover study to compare the psychomotor and cognitive effects of 15 mg Zol with those of 15 mg Dz, 30 mg oxazepam (Ox), 7.5 mg zopiclone (Zop), and ethanol (EOH; 0.65 + 0.35 g x kg(-1)) given to 12 subjects at 1-week intervals. Psychomotor tests (symbol digit substitution, simulated driving, flicker fusion, body sway) were done before and 1, 3.5, and 5 h after intake; immediate and delayed memory were measured between 1.5 and 3.5 h. The plasma concentrations of drugs were measured by gas chromatography and by radioreceptor assay (RRA). The mean values of EOH in blood at 1.5, 4, and 5.5 h were 0.82, 0.88, and 0.6 g x l(-1), and the mean values of RRA-assayed plasma Dz were 470, 330, and 210 microg x l(-1), respectively. The corresponding values of other hypnosedatives, in Dz equivalents (microg x l(-1)), were 550, 750, and 330 for Ox; 350, 270, and 70 for Zol; and 160, 210, and 70 for Zop. The standard RRA graph for Zol was significantly flatter than those for other hypnotics. Zol impaired coordinative, reactive, and cognitive skills at 1 and 3.5 h more clearly than the other agents did, the most sensitive performance (tracking) still being impaired by Zol at 5 h. Dz and Zop were less active than Zol objectively; subjective sedation after Dz and Zol was stronger than after Zop. Compared to placebo, all active agents tended to impair learning and memory, their decremental effects, in declining order, being Zol, Dz > EOH, Ox > Zop. During the delay, Dz and Zol caused similar losses of material that had been learned. When separating "true" delayed memory from immediate memory (attention important), Dz and Zol had equieffects on delayed memory and were more detrimental than Zop. When contrasting that against the impaired psychomotor performances, it is possible that 15 mg Zol impairs memory relatively less than 15 mg Dz does.

Neuropsychological correlates of duration of glances at secondary tasks while driving.

The aim of this study was to find out the neuropsychological measures correlating with overlong glances at secondary in-car tasks while driving. Fifteen. patients with brain damage (without clear neurological or neuropsychological restriction on driving a car) and 11 healthy participants drove a route of 126 km and performed a series of secondary tasks while driving on a highway in an instrumented compact car. Four videocameras allowed detailed analysis of glances during in-car tasks. Neuropsychological measures focused on executive functions, memory, visuospatial skills, and fine motor skills. Moreover, patients' emotional self-evaluation and relatives' evaluation of patients' competencies were included. The proportion of overlong glances away from the road during in-car tasks was greater among the patients than. the healthy drivers. The long glances of the patients correlated strongly with motor and visuospatial deficits, cognitive inflexibility, emotional symptoms, and relatives' evaluations of patients' impaired sensomotor abilities. The results suggest that the frequency of overlong glances was increased by 2 factors: (a) impaired motor and visuospatial skills that evidently caused difficulties in the manipulation of the equipment of the secondary tasks, and (b) impairments of executive functions that were likely to decrease the ability to control the risks related to long glances at the in-car tasks. The slowing of speed during secondary tasks was on the average rather slight and not significantly more pronounced among patients than control drivers, indicating that patients failed to reduce their speed and thus the risk related to prolonged glances at in-car tasks.

Single oral doses of amisulpride do not enhance the effects of alcohol on the performance and memory of healthy subjects.

OBJECTIVES: Amisulpride is a benzamide antipsychotic that binds selectively to dopamine D2- and D3-receptors, preferentially in limbic and hippocampal structures. Since other substituted benzamides have a limited or negligible interaction with alcohol on human performance, amisulpride was studied for this potential. METHODS: In a randomised double-blind crossover study, 18 young, non-smoking men took single oral doses of placebo and amisulpride 50 mg and 200 mg, without and with ethanol (0.8 g. kg-1) taken 30 min later. Objective performance tests and self-ratings were done at baseline and 1.5, 3.5 and 6.5 h after drug intake. Memory (immediate and delayed recall) was tested 2 h after dosing. Breath ethanol and the plasma concentrations of amisulpride and prolactin were measured. Three-way ANOVA + Newman-Keul tests were used for statistical analyses; interactions were confirmed by factorial contrast ANOVA. RESULTS: Mean blood ethanol was 0.94, 0.62 and 0.26 g.1(-1) at the three test times. It produced significant impairment in all performance tests (symbol digit substitution, simulated driving, body sway, flicker fusion, tapping, nystagmus), reduced both immediate and delayed recall in memory tests, and caused subjective clumsiness, muzziness and mental slowness, mainly between 1.5 to 4.5 h after dosing. Amisulpride, 50 and 200 mg elevated plasma prolactin but had minimal or no effect on performance, attention and memory. The decreases in immediate free recall after the 50 mg dose and in delayed free recall after the 200 mg dose were slight. Amisulpride neither modified blood ethanol concentrations nor enhanced the detrimental effect of ethanol on skilled and cognitive performance; it slightly antagonised ethanol in the digit copying test. Ethanol did not modify the effect of amisulpride on plasma prolactin, and the plasma concentrations of amisulpride were little changed by ethanol. CONCLUSIONS: Amisulpride in single oral doses of 50 and 200 mg did not interact significantly with the effects of high, moderate or low concentrations of ethanol on human skilled and cognitive performance. The drugs did interact pharmacokinetically.